Bryan Spring

Physicist uses light to accelerate treatment of drug-​​resistant cancers

by Thea Singer

Pan­cre­atic cancer is a noto­ri­ously treatment-​​resistant dis­ease. Assis­tant pro­fessor Bryan Q. Spring develops pho­to­dy­namic light-​​based ther­a­pies that both target the malig­nant cells and stop the sig­naling between them that sparks new tumor growth. It’s a novel one-​​two punch approach to per­son­al­ized medicine.

With dif­fi­cult malig­nan­cies like pan­cre­atic cancer, you can never kill all the cancer cells with a single cycle of treat­ment,” says Spring, who joined Northeastern’s Depart­ment of Physics in the Col­lege of Sci­ence this past fall. “The sur­viving cells are able to mount a response—they com­mu­ni­cate with one another so they can keep growing, develop resis­tance to the drugs, and thwart the immune system.”

In his latest paper, Spring and his colleagues—in a pre­clin­ical study con­ducted in the lab­o­ra­tory of Tayyaba Hasan at Mass­a­chu­setts Gen­eral Hospital—combined two com­ple­men­tary anti-​​cancer drugs. The first drug, a non­toxic chem­ical, which was acti­vated using light, directly dam­aged the tumor cells and the blood ves­sels feeding them. The second drug, a toxic chem­ical released by that light, “mopped up” the remaining cells’ lines of com­mu­ni­ca­tion, halting regrowth. The study was pub­lished in Nature Nan­otech­nologylast month.

The dual approach not only shrank the tumors by 60 to 90 per­cent in a single cycle but also sup­pressed metas­tasis and lim­ited damage to healthy sur­rounding tissue. In addi­tion, it reduced the dosage of the toxic second drug, says Spring, by “a thou­sand times or more” com­pared to its use alone.

Let there be light

Photomedicine—using light to bring about healing—inspires Spring, who worked under Hasan, a pio­neer in pho­to­dy­namic therapy, as a postdoc. His lab team at North­eastern will draw from bio­physics, bio­med­ical optics and cancer biology to build optical imaging sys­tems. These sys­tems, he says, are “essen­tially minia­ture micro­scopes” that you can insert into the body to visu­alize the pro­teins, or “mol­e­c­ular tar­gets,” sit­ting on indi­vidual cancer cells. Knowing the spe­cific pro­teins on each cell guides the use of tar­geted ther­a­pies and enables cus­tomized cancer treat­ments, just as knowing what bac­terium causes an infec­tion enables cus­tomized antibi­otic treatment.

Pho­to­dy­namic therapy uses optical-​​imaging sys­tems in a variety of ways. In their new study, for example, the researchers com­bined the therapy with a unique light-​​activated drug-​​delivery process to fight advanced pan­cre­atic cancer in mice. The approach could be used against other treatment-​​resistant can­cers as well.

A crossing of disciplines

To start, they devel­oped a nanostructure—an infin­i­tes­i­mally small struc­ture made of fats—to house the two com­ple­men­tary anti-​​cancer drugs. They loaded the non­toxic one in the shell and the toxic “mop­ping up” one in the core, and then deliv­ered the packed nanos­truc­ture intravenously.

The non­toxic drug loaded in the shell made its way inside the tumor. Using optical fibers, Spring trained near-​​infrared light on the tumor, which trig­gered the embedded drug to spew out reac­tive mol­e­cules that killed many of the cancer cells and cut off their blood supply.

Without the second drug, how­ever, the battle may have been lost. That’s because in pho­to­dy­namic therapy within min­utes the reac­tive mol­e­cules also stim­u­late a flurry of com­mu­ni­ca­tion among the remaining cancer cells as they struggle to sur­vive. In fact, these unwanted tumor-​​cell com­mu­ni­ca­tions pro­mote resis­tance to vir­tu­ally all modes of cancer therapy.

Once again, Spring’s light came to the rescue: With impec­cable timing, the light broke down the shell of the nanos­truc­ture, releasing the toxic drug from its core to strike at the com­mu­ni­ca­tion pathways.

Crossing bound­aries like these, in order to merge basic sci­ence with clin­ical appli­ca­tions, is what drew Spring to North­eastern. “There is a great deal of infec­tious enthu­siasm and energy at North­eastern to expand inter­dis­ci­pli­nary research,” he says. “The strong bio­log­ical and med­ical physics pro­grams here are a nat­ural fit for me. Those, com­bined with the nanomed­i­cine, bio­med­ical optics, and bio­engi­neering pro­grams, promise untold research opportunities.”

Originally published in news@Northeastern on February 11, 2016

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